The 10% rate of preterm birth rate worldwide has not been proved amenable to reduction. Avoiding multiple embryo transfer in assisted reproductive technologies (ART) using in vitro fertilization is ...one unassailable method. Preimplantation genetic testing (PGT) to select only a single euploid embryo for transfer is one unequivocal way, maintaining 50%–60% pregnancy rates while avoiding twins. Contemporary methodology entails trophectoderm biopsy of a 5–6‐day blastocyst, and cryopreservation of biopsied embryos while awaiting analysis by next generation sequencing. Embryo biopsy is safe, analytic validity for chromosomal analysis high, and global access to PGT high.
Multiple gestations secondary to transferring multiple embryos in Assisted Reproduction Technology result in preterm birth. This can be avoided by transfer of a single euploid embryo.
This study combines Ordinary Kriging, odor monitoring, and wind direction data to demonstrate how these elements can be applied to identify the source of an industrial odor. The specific case study ...used as an example of how to address this issue was the University Park neighborhood of Portland, Oregon (USA) where residents frequently complain about industrial odors, and suspect the main source to be a nearby Daimler Trucks North America LLC manufacturing plant. We collected 19,665 odor observations plus 105,120 wind measurements, using an automated weather station to measure winds in the area at five-minute intervals, logging continuously from December 2014 through November 2015, while we also measured odors at 19 locations, three times per day, using methods from the American Society of the International Association for Testing and Materials. Our results quantify how winds vary with season and time of day when industrial odors were observed versus when they were not observed, while also mapping spatiotemporal patterns in these odors using Ordinary Kriging. Our analyses show that industrial odors were detected most frequently to the northwest of the Daimler plant, mostly when winds blew from the southeast, suggesting Daimler's facility is a likely source for much of this odor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cell-free DNA reflects both normal and tumor-derived DNA released into the circulation through cellular necrosis and apoptosis. The authors sought to determine the role of preoperative total plasma ...cell-free DNA levels in predicting clinical outcome in patients with ovarian cancer.
After institutional review board consent, DNA was extracted from plasma of 164 women with invasive epithelial ovarian carcinoma (EOC), 49 with benign ovarian neoplasms, and 75 age-matched controls. The samples were randomly divided into training (n = 144) and validation (n = 144) sets. Quantification of cell-free DNA was performed using real-time polymerase chain reaction for beta-globin, and the number of genome equivalents (GE) per milliliter of plasma was determined. Cell-free DNA was correlated with clinicopathologic parameters.
The training and validation sets were similar in terms of demographic features. In the training set, EOC patients had a median preoperative cell-free DNA level of 10,113 GE/mL, compared with patients with benign ovarian neoplasms (median, 2365 GE/mL; P < .0001) and controls (median, 1912 GE/mL, P < .0001). Cell-free DNA >22,000 GE/mL was significantly associated with decreased patient survival (P < .001). After adjusting for other clinical variables, preoperative cell-free DNA >22,000 GE/mL was an independent predictor (P = .02) for disease-specific survival. Analysis of the validation set confirmed significantly higher cell-free DNA levels in EOC (median, 13,672 GE/mL) and that cell-free DNA >22,000 GE/mL was associated with a 2.83-fold increased risk of death from disease (P < .001).
Preoperative plasma total cell-free DNA levels are significantly elevated in patients with EOC. Elevated plasma cell-free DNA is an independent predictor for death from disease in ovarian cancer.
The intent of this study was to evaluate a recent randomized clinical trial evaluating the effect of preimplantation genetic screening (PGS) that reports a negative effect on pregnancy outcome. This ...article reviews appropriate PGS techniques and how they differ from the trial in question. A closer look at the clinical trial in question reveals significant lack of expertise in biopsy, cell fixation, genetic analysis, and patient selection. At most, this trial demonstrates that in inexperienced hands, PGS can be detrimental. No other conclusions concerning the effect of PGS on pregnancy results can be drawn from the trial.
Introduction: Cell-free DNA (CFDNA) is a reflection of both normal and tumor-derived DNA released into the circulation through cellular necrosis and apoptosis. We sought to determine whether ...tumor-specific plasma DNA could be used as a biomarker for tumor burden and response to therapy in an orthotopic ovarian cancer model. Methods: Female nude mice injected intraperitoneally with HeyA8 ovarian cancer cells were treated with either docetaxel alone or in combination with anti-angiogenic agents (AEE788 -- dual VEGFR and EGFR antagonist or EA5 - monoclonal antibody against ephrin A2). Following DNA extraction from plasma, quantification of tumor-specific DNA was performed by real-time PCR using human specific beta-actin primers. The number of genome equivalents (GE/ml) were determined from a standard curve. Apoptosis was assessed by TUNEL staining of treated tumors. Results: The levels of tumor-specific DNA in plasma increased progressively with increasing tumor burden (R2=0.8, p
: Our objective was to compare the levels of total circulating plasma cell‐free DNA (CfDNA) using real‐time PCR in patients with late‐stage ovarian cancer with those in unaffected controls. ...Following IRB consent, DNA was extracted from archived frozen plasma of 19 patients with primary ovarian carcinoma and 12 age‐matched controls using Qiagen DNA Isolation Kits. Quantification of total CfDNA was performed using real‐time PCR with the TaqMan Assay for GAPDH, β‐actin and β‐globin and the number of genome equivalents (GE/mL) were determined from a standard curve. CfDNA levels of these loci were compared between the groups with Student's t‐test, with P < 0.05 being statistically significant. The mean age of the patients was 61.6 years (±9.6) and of the controls was 54 years (±12.2). All patients had high‐grade, advanced stage (III or IV) serous ovarian carcinomas. Preoperative CA‐125 levels ranged from 43 to 15,626 IU/mL (mean 2487.2 ± 3686 IU/mL). Total CfDNA in ovarian cancer was higher among patients with ovarian cancer as compared to controls at all three loci: GAPDH (P= 0.022), β‐actin (P= 0.025), and β‐globin (P= 0.0089). CfDNA is elevated in advanced stage disease compared to controls. These preliminary results suggest that total CfDNA in the plasma of patients with ovarian cancer may be useful for noninvasive screening and disease surveillance.
Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.
We did a systematic review of randomised trials ...comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.
Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk RR 0·78, 95% CI 0·68–0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68–1·01), and oral progesterone (two trials, 183 women; 0·60, 0·41–0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84–1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92–1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15–2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.
Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.
Patient-Centered Outcomes Research Institute.
Current US healthcare delivery systems do not adequately address healthcare demands. Physicians are integral but rarely emphasize prevention as a primary tool to change health outcomes. Home ...visitation is an effective method for changing health outcomes in some populations. The Florida International University Herbert Wertheim College of Medicine Green Family Foundation NeighborhoodHELP service-learning program assigns medical students to be members of interprofessional teams that conduct household visits to determine their healthcare needs.
We performed a prospective evaluation of 330 households randomly assigned to one of two groups: visitation from a student team (intervention group) or limited intervention (control group). The program design allowed randomly selected control households to replace intervention-group households that left the program of their own volition. All of the households were surveyed at baseline and after 1 year of participation in the study.
After 1 year in the program and after adjustment for confounders, intervention group households proved more likely (P ≤ 0.05) than control households to have undergone physical examinations, blood pressure monitoring, and cervical cytology screenings. Cholesterol screenings and mammograms were borderline significant (P = 0.05 and P = 0.06, respectively).
This study supports the value of home visitation by interprofessional student teams as an effective way to increase the use of preventive health measures. The study underscores the important role interprofessional student teams may play in improving the health of US communities, while students concurrently learn about primary prevention and primary care.
To the Editor:
Mastenbroek et al. (July 5 issue)
1
report a detrimental effect of preimplantation genetic screening, performed in women of advanced maternal age, on rates of ongoing pregnancy and ...live birth. We believe this outcome is explained by problems with the authors' methods, both for biopsy and for diagnosis.
As Mastenbroek and colleagues note, pregnancy rates after in vitro fertilization (IVF) steadily decline with increasing maternal age, while rates of pregnancy loss concurrently increase. These observations are attributed mostly to chromosome abnormalities in embryos obtained after follicular stimulation (which range from 50% among young patients to nearly 80% among . . .
Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy
Lois Jovanovic , MD 1 ,
Robert H. Knopp , MD 2 ,
Zane Brown , MD 3 ,
Mary R. Conley , MA 4 ,
Eunsik Park , PHD, MD 4 ,
...James L. Mills , MD 4 ,
Boyd E. Metzger , MD 5 ,
Jerome H. Aarons , MD 6 ,
Lewis B. Holmes , MD 7 ,
Joe L. Simpson , MD 8 and
and the National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group
1 Sansum Medical Research Institute, Santa Barbara, California
2 Northwest Lipid Research Clinic, and the
3 Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
4 Epidemiology and Biometry Branches, National Institute of Child Health and Human Development, Bethesda, Maryland
5 Northwestern University Medical School, Chicago, Illinois
6 Department of Medicine, Magee Women’s Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
7 Genetics and Teratology Unit, Massachusetts General Hospital, Boston, Massachusetts
8 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
Abstract
OBJECTIVE —To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin
requirement.
RESEARCH DESIGN AND METHODS —We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic
women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily
insulin-dose recording, and monthly glycohemoglobin measurements.
RESULTS —In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was
observed between weeks 3 and 7 ( P = 0.000), followed by a significant 9% decline from week 7 through week 15 ( P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7–8 and ending weeks
11–12 ( P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most
frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women
based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2–4 SDs (subgroup 2), and
>4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 ( P = 0.002) and subgroups 2 and 3 together ( P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women.
CONCLUSIONS —Observations in the DIEP cohort disclose a mid–first-trimester decline in insulin requirement in type 1 diabetic pregnant
women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone
secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians
should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of
gestation.
ASI, aggressive subcutaneous insulin
CSII, continuous subcutaneous insulin infusion
DIEP, Diabetes in Early Pregnancy Study
NICHD, National Institute of Child Health and Human Development
Footnotes
Address correspondence and reprint requests to Lois Jovanovic, MD, Sansum Medical Research Institute, 2219 Bath St., Santa
Barbara, CA 93105. E-mail: ljovanovic{at}sansum.org .
Received for publication 22 September 2000 and accepted in revised form 7 March 2001.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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